TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25344	76255;76256;76257	chr2:178570102;178570101;178570100	chr2:179434829;179434828;179434827
N2AB	23703	71332;71333;71334	chr2:178570102;178570101;178570100	chr2:179434829;179434828;179434827
N2A	22776	68551;68552;68553	chr2:178570102;178570101;178570100	chr2:179434829;179434828;179434827
N2B	16279	49060;49061;49062	chr2:178570102;178570101;178570100	chr2:179434829;179434828;179434827
Novex-1	16404	49435;49436;49437	chr2:178570102;178570101;178570100	chr2:179434829;179434828;179434827
Novex-2	16471	49636;49637;49638	chr2:178570102;178570101;178570100	chr2:179434829;179434828;179434827
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGG
• RefSeq wild type template codon: GCC
• Domain: Fn3-72
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.1746
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
R/L	rs556179271	-1.088	0.954	N	0.645	0.478	0.354822389136	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
R/L	rs556179271	-1.088	0.954	N	0.645	0.478	0.354822389136	gnomAD-4.0.0	4.10606E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39754E-06	0	0
R/P	rs556179271	-1.67	0.993	D	0.759	0.488	0.489036454283	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
R/Q	None	-1.166	0.994	N	0.571	0.335	0.300449992093	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.67E-05	0
R/Q	None	-1.166	0.994	N	0.571	0.335	0.300449992093	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	0	3.27783E-04	0	0	0	None	0	0	0	0	0
R/Q	None	-1.166	0.994	N	0.571	0.335	0.300449992093	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
R/Q	None	-1.166	0.994	N	0.571	0.335	0.300449992093	gnomAD-4.0.0	1.48754E-05	None	None	None	None	N	None	0	2.0006E-04	None	0	2.23244E-05	None	0	0	8.47759E-06	0	1.60097E-05
R/W	rs371696090	-0.831	1.0	N	0.703	0.473	None	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	9.81E-05	None	0	8.91E-06	0
R/W	rs371696090	-0.831	1.0	N	0.703	0.473	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.44E-05	0	0	0	0
R/W	rs371696090	-0.831	1.0	N	0.703	0.473	None	gnomAD-4.0.0	6.81864E-06	None	None	None	None	N	None	0	0	None	0	2.23164E-05	None	1.56323E-05	0	2.54328E-06	6.58877E-05	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
R/A	0.9738	likely_pathogenic	0.9681	pathogenic	-2.183	Highly Destabilizing	0.845	D	0.543	neutral	None	None	None	None	N
R/C	0.5304	ambiguous	0.5045	ambiguous	-1.9	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
R/D	0.9964	likely_pathogenic	0.9959	pathogenic	-1.144	Destabilizing	0.975	D	0.742	deleterious	None	None	None	None	N
R/E	0.9594	likely_pathogenic	0.9529	pathogenic	-0.921	Destabilizing	0.845	D	0.467	neutral	None	None	None	None	N
R/F	0.9642	likely_pathogenic	0.9635	pathogenic	-1.351	Destabilizing	0.996	D	0.781	deleterious	None	None	None	None	N
R/G	0.9567	likely_pathogenic	0.9472	pathogenic	-2.51	Highly Destabilizing	0.954	D	0.645	neutral	N	0.511771258	None	None	N
R/H	0.2611	likely_benign	0.2512	benign	-2.259	Highly Destabilizing	0.987	D	0.615	neutral	None	None	None	None	N
R/I	0.9425	likely_pathogenic	0.9273	pathogenic	-1.217	Destabilizing	0.987	D	0.796	deleterious	None	None	None	None	N
R/K	0.2463	likely_benign	0.2304	benign	-1.177	Destabilizing	0.033	N	0.206	neutral	None	None	None	None	N
R/L	0.8636	likely_pathogenic	0.8423	pathogenic	-1.217	Destabilizing	0.954	D	0.645	neutral	N	0.500971157	None	None	N
R/M	0.9064	likely_pathogenic	0.8824	pathogenic	-1.697	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
R/N	0.981	likely_pathogenic	0.9772	pathogenic	-1.302	Destabilizing	0.975	D	0.578	neutral	None	None	None	None	N
R/P	0.999	likely_pathogenic	0.9988	pathogenic	-1.532	Destabilizing	0.993	D	0.759	deleterious	D	0.541485308	None	None	N
R/Q	0.3882	ambiguous	0.35	ambiguous	-1.149	Destabilizing	0.994	D	0.571	neutral	N	0.485852189	None	None	N
R/S	0.9872	likely_pathogenic	0.9847	pathogenic	-2.188	Highly Destabilizing	0.916	D	0.608	neutral	None	None	None	None	N
R/T	0.9725	likely_pathogenic	0.9666	pathogenic	-1.758	Destabilizing	0.975	D	0.691	prob.neutral	None	None	None	None	N
R/V	0.9537	likely_pathogenic	0.9455	pathogenic	-1.532	Destabilizing	0.975	D	0.779	deleterious	None	None	None	None	N
R/W	0.6834	likely_pathogenic	0.6619	pathogenic	-0.87	Destabilizing	1.0	D	0.703	prob.neutral	N	0.500717667	None	None	N
R/Y	0.8731	likely_pathogenic	0.8611	pathogenic	-0.774	Destabilizing	0.996	D	0.77	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.